West Nile Virus Laboratory Testing
The primary diagnostic test for West Nile virus infection is serologic testing for virus-specific IgM antibodies in both serum and cerebrospinal fluid (CSF), with CSF IgM being the gold standard for confirming neuroinvasive disease. 1, 2
Recommended Laboratory Tests
First-Line Serologic Testing
- IgM antibody testing in serum and/or CSF is the primary diagnostic method, with IgM antibodies becoming detectable 3-8 days after symptom onset 1, 2
- CSF IgM antibodies specifically indicate central nervous system infection and are the preferred test for neuroinvasive disease 3, 1
- Serum IgM testing provides faster turnaround time (85.6% of results available by discharge) compared to state health department CSF testing (only 38.1% available by discharge), making it valuable for expediting diagnosis when combined with confirmatory CSF testing 4
- IgG antibody testing should be performed alongside IgM; the presence of IgG alone indicates prior infection rather than acute disease, requiring evaluation for alternative diagnoses 1
Confirmatory Testing Strategy
- Seroconversion between acute and convalescent sera (collected 7-10 days apart) showing conversion to anti-WNV IgM and/or IgG positivity strongly suggests recent infection 1
- Paired serum samples are particularly useful when initial testing is equivocal or when timing of symptom onset is unclear 1
Nucleic Acid Amplification Testing (NAAT)
- NAAT has limited sensitivity (<60%) in immunocompetent hosts but is more sensitive in immunosuppressed patients due to delayed immune response and prolonged viremia 3, 1
- Optimal specimens for NAAT include CSF, plasma, and serum 1
- NAAT should be considered primarily in immunocompromised patients who may lack adequate serologic response 1
Specimen Collection
For Neuroinvasive Disease (Meningitis/Encephalitis)
- CSF is the critical specimen for confirming CNS infection through IgM detection 3, 1, 2
- Serum should be collected simultaneously for IgM and IgG testing 3, 5
- Both specimens should be transported at room temperature within 2 hours 3
Expected CSF Findings
- Pleocytosis is invariably present, with neutrophilic predominance occurring in up to half of patients 6
- Normal CSF does not exclude WNV infection, particularly early in disease course 6
Important Testing Caveats
False Positive Considerations
- IgM antibodies may persist for >6 months (up to 12 months in some cases), potentially causing confusion about timing of infection 3, 1
- Cross-reactivity can occur with recent immunization (Japanese encephalitis, yellow fever vaccines) or other flavivirus infections (dengue, St. Louis encephalitis) 3
- Persistent IgM responses may require revision of current serodiagnostic criteria in some patients 6
Timing Considerations
- CSF IgM may be falsely negative during the first week of symptoms, so repeat testing may be necessary if clinical suspicion remains high 3
- Testing should be performed as soon as WNV infection is suspected, but negative early results do not exclude the diagnosis 1, 5
Special Populations
Pregnant Women
- Screening of asymptomatic pregnant women is NOT recommended due to lack of specific treatments and unclear consequences of infection 1, 7
- Symptomatic pregnant women with meningitis, encephalitis, acute flaccid paralysis, or unexplained fever in areas with ongoing WNV transmission should be tested for WNV antibodies in both serum and CSF 1, 7
Immunocompromised Patients
- NAAT testing is preferred in immunosuppressed patients due to potentially inadequate antibody responses and prolonged viremia 1
- Multiple specimen types (CSF, plasma, serum) should be tested to maximize diagnostic yield 1